HLA -DQ2 homozygosis increases tTGA levels at diagnosis but does not influence the clinical phenotype of celiac disease: a multicenter study

Background and purpose: Magnitude of gluten-specific T-cell responses in celiac disease might be dependent on HLA-DQ2 gene dose. We aimed to investigate the effects of HLA-DQB1*02 allele dose on clinical outcomes. Methods: We reviewed the charts of all celiac patients attending to three Hungarian university clinics after 1997 and included those patients, who 1) were diagnosed with celiac disease, 2) underwent high resolution HLA-typing, and 3) were ≥18 years at the time of data collection. HLA typing was performed to determine DQB1*02 allele dose. Patients were divided into risk groups by DQB1*02 allele dose, as follows: high-, intermediate-, and low-risk groups corresponded to a double, single, and zero doses, respectively. We used ANOVA and Person’s chi-squared test to explore association between HLA-risk and clinical variables. Results: 727 celiac patients attended the clinics but only 105 (14.4%) patients were eligible for inclusion. High, intermediate, and low HLA-risk patients comprised 35.3%, 52.3%, and 12.3% of the study population, respectively. Double dose of HLADQB1*02 was more frequent in patient with high tTGA level (> 10 times the upper limit of normal) (p=0.045). Gene dose was not associated with younger age at diagnosis (p=0.549), gender (p=0.739), more severe diagnostic histology (p=0.318), more frequent classical presentation (p=0.846), anemia (p=0.611), metabolic bone disease (p=0.374), dermatitis herpetiformis (p=0.381), and autoimmune diseases (p=0.837). Conclusions: Our study shows a significant gene dose effect in terms of tTGA level at diagnosis, but no significant association between HLA-DQB1*02 allele dose and the clinical outcomes in celiac disease